James Muller, M.D., joins the Board of Directors at ClinicalTrialsWiki.org

We are honored to welcome Dr. James Muller, renowned cardiologist and one of three co-founders of an organization that won the 1985 Nobel Peace Prize, to our Board of Directors. His bio follows:

James E. Muller, M.D., was one of three American Co-founders of the International Physicians for the Prevention of Nuclear War (IPPNW) the organization awarded the 1985 Nobel Peace Prize.

Dr. Muller currently serves as CEO of InfraReDx, Inc, a company that has developed a near-infrared spectroscopy catheter for the identification of lipid-rich and presumably vulnerable coronary artery plaques.

Dr. Muller formerly served as a Professor of Medicine at the Harvard Medical School where he conducted research for over 25 years on the causes of heart attacks. In 1994, he introduced the term "vulnerable plaque" to describe those plaques likely to disrupt and cause disease onset. He co-founded InfraReDx in 1998 after a detailed search to find the optimal technology to identify lipid-rich coronary artery plaques.

Jeff Drazen, M.D., joins the Board of Directors at ClinicalTrialsWiki.org

Dr. Drazen has been a mentor and friend to us for many years in the H.S.T. program at Harvard Medical School.

We extend a warm welcome to Dr. Drazen as he joins our Board of Directors today. His full bio follows:

A specialist in pulmonology, Jeffrey M. Drazen, M.D., maintains an active research program. Dr. Drazen has published more than 300 articles on topics such as lung physiology and the mechanisms involved in asthma. In 1999, he delivered the Amberson Lecture, the major research address at the annual meeting of the American Thoracic Society. In 2000, he received the Chadwick Medal from the Massachusetts Thoracic Society for his contributions to the study of lung disease.

Dr. Drazen is the Distinguished Parker B. Francis Professor of Medicine at Harvard Medical School, professor of physiology at the Harvard School of Public Health, and senior physician at the Brigham and Women’s Hospital. In 2003, he was elected as a member of the Institute of Medicine. Dr. Drazen has served on numerous committees for the National Institutes of Health: the Respiratory and Applied Physiology Study Section; the Lung Biology and Pathology Study Section; the Pulmonary Disease Advisory Council; and the National Heart, Lung, and Blood Institute Advisory Council. He currently serves as the co-chair of the Institute of Medicine Drug Forum and is a member of the advisory group to the World Health Organization International Clinical Trials Registration Platform.

Dr. Drazen joined the New England Journal of Medicine as editor-in-chief in July 2000. At the Journal, Dr. Drazen’s responsibilities include oversight of all editorial content and policies. His editorial background includes service as an associate editor or editorial board member for the Journal of Clinical Investigation, the American Journal of Respiratory Cell and Molecular Biology, and the American Journal of Medicine.

Dr. Drazen earned his bachelor’s degree and graduated summa cum laude from Tufts University. He received his medical degree from Harvard Medical School and completed his internship and residency at Peter Bent Brigham Hospital in Boston. Dr. Drazen received honorary degrees from the University of Ferrara, Italy, and the National and Kapodistrian University of Athens, Greece.

A native of Missouri, Dr. Drazen lives with his wife in Winchester, Massachusetts. They are the parents of two grown sons.

Warner Slack, M.D., joins the Board of Directors at ClinicalTrialsWiki.org

We are delighted to welcome a second distinguished clinician to our Board of Directors today, Warner Slack, M.D.

Dr. Slack brings us over 35 years of experience in health information technology. He is currently co-president of the Center for Clinical Computing and, during his medical training, helped develop one of the world's first electronic health record (EHR) systems. His full bio follows:

Dr. Slack received his bachelor's degree from Princeton University, his medical degree from Columbia University's Columbia University's College of Physicians and Surgeons, and his residency training in neurology at the University of Wisconsin. Over the past 35 years he has focused his research on the use of computers to improve communication in medicine and to empower both doctors and patients for better health care. His early work in computer-based medical interviewing at the University of Wisconsin led to the first study of patient-computer dialogue.

Over the years, he has established new computer-based approaches to the medical interview, and developed and studied programs that provide direct assistance to the patient in the management of common, important medical and psychological problems. He was an early advocate of the patient's right to participate in decisions about diagnosis and treatment.

Dr. Slack and his colleagues at the Center for Clinical Computing (CCC) and the Harvard Medical School, have developed, implemented, and studied an integrated, hospital-wide clinical computing system (the CCC system) which is used in patient care at Boston's Beth Israel Deaconess Medical Center and Brigham and Women's Hospital. Distinguishing features of the CCC system are the unparalleled intensity and extensiveness of its use by clinicians in the care of their patients and the substantial financial benefits that have been realized in conjunction with its use.

Dr. Slack is Professor of Medicine at Harvard Medical School and, with Dr. Howard L. Bleich, co-president, of the Center for Clinical Computing and co-director of the Division of Clinical Computing, Department of Medicine, Beth Israel Deaconess Medical Center.

Among his recent publications, Dr. Slack is the author of Cybermedicine: How Computing Empowers Doctors and Patients for Better Health Care (revised and updated edition, San Francisco: Jossey-Bass, 2001).

Edward Hundert, M.D., joins the Board of Directors at ClinicalTrialsWiki.org

We are delighted to welcome Dr. Edward Hundert, M.D., former President of Case Western Reserve University, to the Clinical Trials Wiki family, and as a member of our Board of Directors. His bio is below:

Dr. Hundert is an internationally known academic leader, scholar, educator, psychiatrist, and medical ethicist. Over the past 20 years, he has served as President of Case Western Reserve University, Dean of the University of Rochester School of Medicine and Dentistry, and Associate Dean for Student Affairs at Harvard Medical School. He has held professorial appointments in psychiatry, medical ethics, cognitive science, and medical humanities, and he is a leader in developing innovative institutional affiliations and curricula both in academic medical centers and across all levels of higher education.

Dr. Hundert earned his bachelor’s degree in mathematics and the history of science and medicine, summa cum laude, from Yale University, where he received Yale’s Chittenden Prize “to the graduating senior with highest standing in mathematics or the natural sciences.” He attended Oxford University as a Marshall Scholar, receiving the Batterby Prize from Hertford College for “highest first class honours in philosophy, politics and economics.” Four years later he earned the M.D. from Harvard Medical School, receiving the Sanger Prize for “excellence in psychiatric research.” He completed his psychiatric residency at McLean Hospital, a Harvard affiliate, where he served as chief resident. He has received numerous teaching, mentoring, and diversity awards, and for six consecutive years he was voted the “faculty member who did the most for the class” by Harvard Medical School graduates.

Dr. Hundert has served on many national boards, including the Association of American Universities, the American Association of Medical Colleges, and the Liaison Committee on Medical Education. He co-chaired the Institute of Medicine’s National Summit on Health Professions Education. Dr. Hundert has served as chair of the Ethics Committees of McLean Hospital and the Massachusetts Psychiatric Society, and also served as ethics column editor for the Harvard Review of Psychiatry. Dr. Hundert has written dozens of articles and chapters on a variety of topics in psychiatry, philosophy, medical ethics, and medical education, as well as two books: Philosophy, Psychiatry and Neuroscience: Three Approaches to the Mind (Oxford University Press, 1989), and Lessons from an Optical Illusion: On Nature and Nurture, Knowledge and Values (Harvard University Press, 1995).

In addition to his work in the Division of Medical Ethics, Dr. Hundert is a member of the boards of TIAA-CREF and the Rock and Roll Hall of Fame.

Two new additions to our Board of Directors

We're pleased to announce the addition of Warner Slack, M.D., and Edward Hundert, M.D., to our Board of Directors. Both of these distinguished clinician-educators share our vision for a fully transparent, non-commercialized source of clinical trials information and opinion.

We are fortunate to count them among the Clinical Trials Wiki family.

Full bios of each new Board member will be posted shortly on this blog and our main site, ClinicalTrialsWiki.org.

Health IT: the new Apollo program?

Yesterday, Mark Leavitt over at THCB compared the portion of Obama's "American Recovery and Reinvestment Act" dealing with electronic health records (EHR) to Kennedy's program to send a man to the moon. Sound far-fetched?

Here's the quote (full article after the jump):

I’m personally struck by the parallels to a historical event still vivid in my memory: Project Apollo, President Kennedy’s incredible national goal of achieving manned spaceflight to the moon.

Apollo cost $22B (in 1969 dollars, now worth five times that) and took 8 years to achieve the first moonwalk. NASA, a new government agency, spearheaded the effort, but the technology was developed by private sector contractors.

The health IT provisions of ARRA invest at least $35B to incentivize full EHR deployment, allowing 5-7 years to reach that goal – remarkably similar to Project Apollo. The Office of the National Coordinator (ONC) has been codified and funded to lead the effort, and just as in the case of Apollo, I expect much of the work will need to be accomplished by contractors in the private sector -- CCHIT included, of course, provided we quickly “grow up” to meet the enlarged responsibilities.

While EHR won't induce the sort of national high drama that the Apollo program did (I can see eyeballs rolling already...), Mark does have a point about the similar scale and impact of the two projects. Arguably, EHR will actually have far greater impact, through the improved patient outcomes that result from increased accessibility, consistency, and comprehensiveness of our new health records.

Yet until recently, EHR was hardly brought up in the national discourse about high-impact fixes to improve health care. James Holsinger, in all his bespectacled charm, never once mentioned the issue during his prolonged confirmation process for U.S. Surgeon General in '07.

As Mark rightly points out, the thorniest issues surround adoption of new EHR technologies -- getting a physician to give up old patterns of behavior (see NHS's initiative in England to banish white coats) may prove harder than shooting the moon.

Our new Facebook home

Yesterday morning, I created a new Facebook group to coincide with the launch of our new website. So far it's Gaurav, myself, and 12 good friends. Brice, we think, is trapped in the bowels of the ICU and hasn't had a chance to join yet!

Here's how we describe ourselves on Facebook:

ClinicalTrialsWiki.org strives to be the most trusted source of clinical trials information online. You can search our database of analysis and opinion on over 65,000 clinical trials.

We're structured as a 100% volunteer-run, 501(c)(3) nonprofit and, as a policy, we don't accept ads or money from the pharmaceutical and medical device industries.

That's all there is to it -- no ads, no gimmicks, and no tricks up our sleeve.

The site was developed by three friends at Harvard Medical School and M.I.T.

We'd love to see you join our community!

Whew!

I think I speak for the entire team at ClinicalTrialsWiki.org when I say that we're thrilled to have a new, far more functional site go live today. Everyone here has been working feverishly over the last 72 hours to get this work done, though it's just the beginning.

To his credit, Brice has been on call in the ICU and several times decided to get work done with us post-call instead of going to sleep. And this weekend, Gaurav heroically led our webcrawler development effort though his new fiancee flew into town for the weekend! Both of my teammates continue to inspire me with their passion for this project.

Here are a few highlights of our achievements over the last few days:

• We designed and implemented a Wikibot to automate the extraction of data from ClinicalTrials.gov
  
• We laid out a brand new format for our clinical trials 'data' page
• We decided on a new logo, color scheme, and website layout
• We met with friends and colleagues at HMS, the Countway medical library, and HealthMap to get feedback on our ideas and refine our thinking about the site
• We've set up meetings with NEJM and FDA to discuss possible partnership and site integration

Every minute as I write this, our crawler is adding 5-10 new fully populated clinical trials to our site. Look for even more changes to come, particularly as we enhance the usability of the wiki features of the site, so that anyone on the web can edit articles and upload data files.

We're committed to being 100% transparent with you about how we develop and maintain our site. We know you might have ideas about where we should go from here, and we want to hear from you.

WikiBot is Online

After a weekend of hacking php (and with the help of the fantastic source code of BasicBot), we've finished our first database-browsing, wiki-populating, automated bot which will populate the wiki with content and expert pages for all 65,000 trials on the clinicaltrials.gov database. The bot is chugging along diligently, and we expect to have completed the population process by mid-week.

In the future, we're planning on creating a multi-threaded bot that will speed up the process tremendously, as well as limiting updates to new or revised content from clinicaltrials.gov. For now, we're just excited that we'll soon have more content than we'll know what to do with -- ready and waiting for your discussion and analysis!

On the aesthetics front, we're continuing to modify the layout of individual content pages to make it as easy as possible to navigate the plethora of data and find the information you're looking for. As always, we'd love your feedback and suggestions.

If you're curious, you can see the trials being added in real-time by the bot on the "New Pages" list.

Version 2.0 is Live!

ClinicalTrialsWiki.org has finally gotten a much-needed aesthetic overhall -- the first of many revisions, I am sure. It's a work in progress, so please leave your feedback.

We're also putting the final touches on an automated PHP crawler bot that will keep every trial on ClinicalTrialsWiki in sync with the ClinicalTrials.gov repository, and ensure that all of the information is up-to-date.

Things are exciting around here, and I can feel the momentum building!

Supreme Court rules on different standards for drug and device makers

Does a patient who's undergone implantable cardioverter-defibrillator (ICD) placement, and whose ICD's electronic components have now failed -- requiring emergent device replacement -- have the right to sue the cardiac device's maker for negligence, if he was repeatedly warned by his cardiologist of the well-known risk of post-implantation electronics failure?

Device makers have long argued 'No': every device has risks, and the FDA-CDER premarket approval process is designed to weigh risk against benefit before permitting the introduction of a new device. The Supreme Court last year substantially agreed with this view in Reigel v Medtronic by ruling that successfully obtaining premarket approval from the FDA gives medical device makers (in this case, Medtronic, a manufacturer of ICDs) a strong defense against lawsuits filed in state courts because federal regulation "pre-empts" state law here.

Today, under presumably different logic, the court ruled in Wyeth v. Levine that drug makers can be sued in state courts, even when they have obtained FDA approval.

So why the discrepancy? The Wall Street Journal Health Blog reports on the issue today:

The 8-1 ruling in the medical device case, Riegel v. Medtronic, relied heavily on the “Medical Device Amendments” signed into law in 1976.

As the court wrote in Riegel:

The MDA provides that no State ‘may establish or continue in effect with respect to a device . . . any requirement’ relating to safety or effectiveness that is different from, or in addition to, federal requirements …

That language goes to the heart of preemption, the legal question at issue in both cases: Does federal regulation override state law? In the case of devices, the court found, MDA explicitly preempts state law.

But the MDA is all about devices, while the case decided today, Wyeth v. Levine, is all about drugs. The relevant drug law is the Food, Drug, and Cosmetic Act, enacted in 1930 and amended several times in the decades since then.

Amendments added in 1962 indicated “that a provision of state law would only be invalidated upon a ‘direct and positive conflict’ with the FDCA,” Justice Stevens wrote in his majority opinion in Wyeth v. Levine.

What’s more, Stevens added, “when Congress enacted an express pre-emption provision for medical devices in 1976″ — in the MDA — “it declined to enact such a provision for prescription drugs.”

The notion of pre-emption gets to the very heart of our national experiment with federalism, and makes for a fascinating legal discussion. But it's unfortunate for most Americans that this case hinged on the issue of pre-emption, rather than addressing the broader social ramifications of an increase in state and federal drug lawsuits in our already litigation-littered society.

Something just doesn't sit well with me about our asymmetric policy for dealing with device and drug companies (largely for historic reasons related to the recency of most device legislation, and the relative strength of industry lobbying groups). We've long been doing this to our detriment, I think, in the FDA's 510K process of rapidly approving "substantially equivalent" devices.

Medical device and pharmaceutical companies face enormous legal liability and financial risk in developing the innovative therapies that physicians and patients rely upon.

So there's a few reasons why I agree with the Court's original decision in Reigel v Medtronic:

• First, mitigating the legal liability to device companies removes downward pressure on innovation;
• Second, the tort system in our country is badly broken, with punitive damages awarded by juries in many cases exceeding the pale of reason;
• Third, I'm hoping this decision will spur legislation to give FDA broader oversight and stricter controls over device development and postmarketing surveillance.

If we're answering the question of whether the companies have been negligent, and we ask -- did their actions "cause" the damages suffered, and could a "reasonable person forsee the harm" to the patient in this case? -- then I think the answer to both questions is yes.

However, drugs and devices, by virtue of their intimate relationship with our bodies, have the potential to cause immense, sometimes irreversible, harm. We can predict, and warn about the dangers of, this harm by conducting preclinical and clinical trials.

Our regulatory process should (in the ideal world) weed out those drugs or devices whose risk/benefit profile is tipped towards risk, and protect companies and physicians who adequately educate patients about that risk prior to starting treatment. Otherwise life-saving therapies would never see the light of day for fear of a class-action lawsuit.

HMS featured in NYT article today

Today's most popular NYTimes article features Harvard Medical School's conflict-of-interest policy and ties to the pharmaceutical industry.

Read the full article here.

The team at ClinicalTrialsWiki.org is currently composed of fourth-year students at Harvard Medical School. We believe our site can go a long way towards promoting transparency and nonbias in medical education.

Kudos to the students who've been featured in the article for the work they are doing.

Don't mix PPIs and Plavix...
How many patients are not on a PPI these days?...should they be?

A retrospective study published in JAMA this week strongly suggests that one should be careful when prescribing PPIs upon discharge of patients hospitalized for an acute coronary syndrome (ACS). When comparing the use of a PPI in patients with ACS taking clopidrogel after discharge, Michael Ho et al. found that patients taking clopidrogel and prescribed a PPI had a higher risk of death or rehospitalization for recurrent ACS than those who were taking clopidrogel alone (Adjusted odds ratio 1.25 CI[1.11-1.41]) (1). The results of this study are supported by several translational and mechanistical studies showing that the use of PPIs reduces the antithrombotic effects of clopidrogel (2), (3).

Maybe all of us future interns should follow our pharmacology professor's suggestion to place a bottle of Omeprazol pills under each patient's pillow on the wards. That way, when asked by a tired junior resident to put Mr. Jones on a PPI, we can safely say that he's already "on" it...

(1) P. Michael Ho et al. JAMA. 2009; 301(9): 937-944
(2) Gilard M. et al. J. Thromb Haemost. 2006; 4(11): 2508-2509
(3) Gilard M et al. J Am Coll Cardiol. 2008; 51 (3): 256-260

Redesign of main wiki page

The main wiki page at ClinicalTrialsWiki.org is now much richer with content, which we'll continue to update on a daily basis. This is what it looks like on my home computer:

After hacking around with the MediaWiki source code (compliments of Matthew Burton's free help page), we've also configured a new 'expert' tab on all of our content articles (i.e., clinical trial pages). Look for expert commentary to populate these tabs in the coming weeks.